The extended chemical defensome: emphasizing mechanisms of defense as key research avenues to tackle priority questions in environmental toxicology

Chemical pollution threatens organismal integrity, affecting growth, reproduction, behavior, and overall fitness, ultimately leading to shifts in biodiversity and the provisioning of ecosystem services. In response to chemical exposure, organisms use specific regions of their genome coding for different defense mechanisms-this collection of genes is termed the "chemical defensome." Specifically, genes associated with efflux transporters, transcription factors, antioxidant systems, and biotransformation pathways, among others, are expressed to reduce toxicity. These sub-individual processes are, for the most part, widely conserved across taxa and play a critical role in enabling organisms to cope with polluted environments. Additionally, we argue that behavioral responses-particularly spatial avoidance-should be recognized as an individual-level defense mechanism and incorporated into an extended chemical defensome framework. Expanding and reinforcing the concept of the chemical defensome beyond traditional studies at the genome level, as well as developing strategies to synthesize existing data, offers a valuable opportunity to link gene composition to physiological and behavioral responses, thereby addressing key research needs in environmental toxicology. These include estimating the impact of chemical mixtures across different exposure scenarios, identifying the main drivers of intra- and interspecific sensitivity to pollution, and assessing large-scale ecological processes, such as biodiversity losses, in polluted habitats in a more integrated manner. In ecotoxicology and environmental risk assessment, understanding not only how chemical pollutants exert toxicity but also how organisms counteract these effects is essential. Indeed, investigating chemical-induced shifts in defense mechanisms can improve predictions of adverse outcomes at higher levels of biological organization and can inform more effective chemical management and regulatory strategies.