Genome-Wide Association Reveals Signalling-Linked Infection Tolerance in Hibernating Bats

Hibernation profoundly alters host-pathogen dynamics by suppressing metabolism and immune function, posing unique challenges for infection control. In this study, we examined how genomic variation modulates infection and physiological traits in temperate bats during hibernation. We combined infection screening, haematology, blood biochemistry, and whole-genome sequencing across five vespertilionid species, identifying over 170,000 single nucleotide variants (SNVs) and assessing their associations with 23 health-related variables. Using the phylogenetically informed treeWAS framework, we detected 515 significant SNVs linked to traits including fungal, protozoan and bacterial infections, acid-base balance, and blood cell indices. These SNVs mapped to 137 unique genes, which were enriched for functional domains related to cytoskeletal dynamics, membrane trafficking, and intracellular signalling (e.g., SH3, C2, BAR, semaphorin). Notably, canonical immune effector genes were underrepresented, and several trait-associated SNVs appeared in blocks across multiple scaffolds, pointing to regulatory loci as key modulators of hibernator health. Our findings support the hypothesis that bats rely on infection tolerance rather than resistance during hibernation, with genomic variation in regulatory and signalling pathways shaping their physiological responses to infection under energy-limited conditions.