FKBP5 expression in Peromyscus leucopus reflects land cover and climate predictability.

Anthropogenic activities such as urbanization, agricultural expansion, and climate change create landscapes of stress for wildlife. In vertebrates, neurophysiological stress responses are regulated by the hypothalamic-pituitary-adrenal (HPA) axis, with the co-chaperone FKBP5, playing a key role in modulating glucocorticoid receptor (GR) sensitivity through negative feedback. Variation in FKBP5 expression influences how individuals cope with stressors (i.e., endocrine flexibility): lower FKBP5 expression is associated with more efficient activation and termination of stress responses, whereas higher expression weakens negative feedback and prolongs HPA-axis activity. Here, we examined how FKBP5 expression in blood relates to land cover (e.g., natural and anthropogenic) and climate predictability (Colwell's indices of temperature and precipitation) in white-footed mice (Peromyscus leucopus), a non-commensal rodent that serves as the primary reservoir host for Borrelia burgdorferi. Using samples from 126 mice captured across 12 NEON (National Ecological Observatory Network) sites and characterizing land cover composition using principal component analysis (PC1 captured 54% of variance, loading positively for tree cover and negatively for grass, cropland, shrub, and built cover), we found forest-dominant sites (higher PC1) predicted elevated FKBP5 expression in blood. We also found that sites with increasingly predictable precipitation predicted lower FKBP5 expression, indicating greater endocrine flexibility being favored in predictable environments. While unexpected, the positive association between FKBP5 expression and increasing tree cover suggests natural P. leucopus habitat may induce prolonged HPA activation due to local ecological conditions such as predation or competition. Future work should address how individuals vary in FKBP5 over time and during stressful events.