Emerging zoonotic diseases such as influenza A viruses (IAVs) and coronaviruses increasingly highlight the complex interactions between pathogens; their human, livestock and wildlife hosts; and ecological drivers. One major environmental factor that may impact virus emergence is from the effects of diverse chemical pollutants released into ecosystems by human activity. Given their diversity and complex mixed nature, the impact and mode of action of many pollutants remains unknown but could be important player in zoonotic risk assessment. Here, we lay the foundations for study and screening of chemical pollutants on viral infections using the model environmental contaminant, lead (Pb). We test the interactions between lead compounds on cell health, IAV infection and growth, and antiviral immune signalling in human and canine cell lines. Initial results indicate a clear dose-dependent cytotoxic effect of lead in both cell lines associated with morphological changes, particularly at low seeding density. Contrastingly, under standard viral infection conditions, virus replication appears relatively unchanged. To assess the in vivo relevance of our findings, ongoing viral metagenomics of wild mammals from high and low lead areas is being carried out to investigate associations between pollutant exposure and pathogen prevalence. We are focusing on the Eurasian otter (Lutra lutra), a sentinel species within the order Carnivora and a known host of zoonotic viruses like highly-pathogenic avian IAV. By integrating cellular and ecological data, this interdisciplinary research aims to addresses key knowledge gaps inform future One Health initiatives to mitigate zoonotic risks relevant for lead and other chemical pollutants.