(A) Enriched biological processes related to DNA repair pathways including homologous recombination (GO:0000725), base excision repair (GO:0006284), nucleotide excision repair (GO:0006289) and mismatch repair (GO:0006298). (B) A protein interaction network generated using STRING of genes differentially expressed in the Homologous recombination pathway (KEGG: 03440)³⁹. (C) Enrichment map cluster of upregulated gene sets relating to DNA repair processes. (D)Enrichment map cluster of downregulated metabolic processes.

(A) Enrichment map of genes upregulated in response to radiation showing GO terms related to carbohydrate metabolism. (B) GO terms upregulated in response to radiation, showing enrichment of several immune-related processes such as lymphocyte, leucocyte, and T cell activation (generated using Enrichment map). (C)Enrichment map of genes upregulated in response to radiation showing changes in lipid transport. (D) Protein interaction map generated using STRING of genes from the GO term of immune effector process GO term (GO:0002699) (red) with genes from the response to fibroblast growth factor (GO:0071774) (blue). (E) iPathwayGuide network constructed with genes from the Immune processes GO term and BP terms related to ECM and fibroblast activation.

(A) Gene expression in the induced torpor + radiation (18.5-mel-rad) group compared to that in the control (28.5-Ctrl) group. The figure shows the relative increase in AMD1 (p = 0.012), GTP1 (p = 0.034), ODC1 (p = 0.309), and MTA1 (p = 0.0022) expression compared to the control. ODC1 shows a trend towards increased expression in the torpor + radiation group vs control (28.5-Ctrl). CDK19 shows decreased expression compared to the control group (p = 0.05) *p ≤ 0.05 and ** ≤ 0.01. (B) Enrichment map showing that genes related to DNA repair-related biological processes such as homologous recombination are upregulated relative to the control group. (C) Bar plot showing differential expression of DNA repair process genes in induced torpor + radiation vs control. BARD1 and PARPBP show strong upregulation in the induced torpor + radiation condition.

Genes correlated with locomotor activity scores in the radiation and torpor + radiation groups. This schematic shows that increased activity scores in the radiation group are correlated to an upregulation of genes involved in biological processes such as nucelotidase activity, Golgi transport and phagocytosis, and a downregulation of growth, endocytosis, aminoacylation and heparin catabolism related genes. Genes correlated with lower activity scores in the group are associated with immune-related processes such as hemopoiesis, mononuclear cell differentiation, and B cells receptor signalling. In the torpor + radiation group genes correlated with higher activity scores are associated with VEGF expression, exocytic vesicles, and double strand break repair. Genes correlated with decreased activity are correlated with ECM, actin nucleation, creatine biosynthesis and inositol phosphate and a downregulation of genes involved in aminoacylation, amino acid metabolism, B cell receptor activation and chromatin binding. Created with BioRender.com.

(A) Comparison of zebrafish torpor and hibernating bear genes. A heat map of the 54 shared genes between the zebrafish torpor group and the hibernating bear showing their direction of expression relative to the active controls (B) Heat map of the 52 shared genes between the zebrafish radiation group and the space flown mouse liver showing their direction of expression (red = upregulated, blue = downregulated).

Comparison of our zebrafish radiation group vs space flown mouse and the zebrafish induced torpor group vs hibernating bear. The results between the zebrafish radiation model and the space flown mouse show shared upregulation of genes involved in sulphur dioxygenase activity, telomerase RNA reverse transcriptase, alpha-sialidase activity, and fibroblast growth factor receptor activity. Shared downregulated genes included the estrogen receptor (ESR1), and genes involved in cytoskeleton formation and cellular migration. Additionally, shared biological processes included lipid metabolism and response to endogenous stimuli. Comparison of the torpor group versus the hibernating bear showed shared upregulation of anti-apoptotic genes, DNA repair genes, pro-survival genes, antioxidant genes, and Wnt signaling. Shared downregulated genes included anticoagulant genes, while dysregulated genes were involved in lipid oxidation and cholesterol synthesis. Furthermore, shared BP included a response to ROS, cell cycle checkpoints, telomere lengthening, and nitric oxide synthase. Created with BioRender.com.