Seasonal trade-offs shape metabolomic and proteomic responses to Varroa destructor parasitisation in honey bees (Apis mellifera)

The ectoparasitic mite Varroa destructor is a major driver of honey bee mortality, yet its effects depend on the contrasting seasonal phenotypes of worker bees. We applied an integrated metabolomic and proteomic approach to dissect how Varroa parasitisation affects the molecular physiology of short-lived summer and long-lived winter bees. Newly generated summer data were integrated with a previously published winter dataset, enabling direct seasonal comparison under identical analytical pipelines. Season represented the dominant source of molecular variation; however, Varroa parasitisation elicited coherent but phenotype-dependent responses. In summer bees, parasitisation was associated with elevated post-emergence mortality and a pronounced metabolic shift characterised by altered purine turnover, membrane lipid remodelling and reduced tricarboxylic acid cycle throughput. These metabolomic changes were mirrored by proteomic changes in the abdomens indicative of stress-associated catabolism, mitochondrial dysfunction and reduced anabolic capacity. In contrast, winter bees exhibited limited metabolic plasticity but showed selective depletion of antioxidant enzymes, simple carbohydrates and nutritional proteins, consistent with impaired longevity-associated maintenance and nutrient allocation. Proteomic analysis of heads revealed a broader response than abdomens. In summer bee heads, Varroa parasitisation redirected investment towards membrane trafficking, transport and regulatory control at the expense of metabolic, sensory and secretory functions. Heads of Varroa-parasitised winter bees showed reduced abundance of immune, sensory and nutritional proteins, including vitellogenin. Our results demonstrate that V. destructor does not elicit a uniform stress response but exploits seasonally distinct physiological states of honey bees, generating divergent molecular stress patterns with direct implications for worker survival and colony resilience.