A neonicotinoid pesticide causes tissue-specific gene expression changes in bumble bees

Pesticides often harm beneficial insect pollinators, impairing their ability to navigate the environment, learn, fight off disease, and reproduce. Understanding the mechanisms underlying these disorders is essential for improving pesticide risk assessments. To test whether pesticide exposure induces similar or distinct transcriptional responses across tissues, we administered a field-realistic dose of the common neonicotinoid clothianidin to Bombus terrestris bumble bees. We then measured gene expression in brains, hind femurs, and Malpighian tubules. Our analyses revealed that 82 % of gene expression differences were tissue-specific. Although genes associated with energy metabolism were consistently down-regulated across all tissues, pesticide exposure primarily affected core tissue functions, namely genes linked to ion transport in the brain, muscle function in the hind femur, and detoxification in Malpighian tubules. Furthermore, while the brain holds the highest abundance of pesticide target receptors, other tissues showed more substantial differences in gene expression magnitude. These findings reveal that pesticide exposure causes complex, tissue-specific effects rather than a uniform body-wide response. Our study provides a mechanistic basis for the severe effects of pesticide exposure on bees and shows how transcriptomics can help pinpoint the most affected areas and processes across the body. Aligning toxicological assays with these findings could significantly improve the precision of pesticide safety evaluations. • Chronic exposure to the neonicotinoid pesticide clothianidin causes gene expression changes in bumble bees, with effects varying across tissues (brain, Malpighian tubules, and hind femur). • Energy metabolism is impacted across all tissues, all other changes are tissue-specific. • These changes disproportionately affect genes that are highly active in a given tissue. • The magnitude of gene expression changes is lower in the brain compared to other tissues, suggesting the brain may be less affected in terms of response intensity. • Tissue-specific expression changes provide insight into organism-wide effects of pesticides and may explain the complex effects of exposure on bees at the organismal level.