| Description: |
Honey bees ( Apis mellifera ) are vital pollinators in fruit‐producing agroecosystems like highbush blueberry (HBB) and cranberry (CRA). However, their health is threatened by multiple interacting stressors, including pesticides, pathogens, and nutritional changes. We tested the hypothesis that distinct agricultural ecosystems—with different combinations of agrochemical exposure, pathogen loads, and floral resources—elicit ecosystem‐specific, tissue‐level molecular responses in honey bees. We conducted an integrated multi‐omics analysis using RNA‐sequencing (RNA‐seq), proteomics, and gut microbiome profiling across three key tissue types (head, abdomen, and gut) of honey bees collected from two agroecosystems over two field seasons. Quantification was performed for pesticide residues, pathogen loads ( Nosema spp., Varroa destructor , and multiple viruses), and gut microbiota. Weighted gene co‐expression network analysis (WGCNA) revealed tissue‐specific protein modules with ecosystem‐associated patterns, which differed from RNA co‐expression networks. Microbiome composition also varied, with key genera like Gilliamella, Snodgrassella, and Bartonella correlating with metabolic modules. These findings underscore the complex, environment‐dependent impacts of agroecosystem conditions on bee health. Our study provides a system‐level understanding of how combined pesticide, pathogen, and parasitic stressors, mediated by diet and microbiome, shape molecular phenotypes in honey bees—informing strategies for pollinator protection in managed landscapes. Summary This study provides a comprehensive multi‐omics analysis of honey bees foraging in blueberry and cranberry agroecosystems, offering novel insights into the molecular mechanisms underlying pollinator health in managed crop environments. By integrating transcriptomic, proteomic, and microbiome profiling across key tissues—head, abdomen, and gut—we reveal how environmental stressors, including pesticide exposure, pathogen infections, and parasitic infestations ... |