Abstract Livestock workers are at the frontline of exposure to agriculture-generated bioaerosols containing a diverse mixture of respiratory pathogens. The misuse and overuse of antibiotics in agriculture has been posited as a potential driver in the accelerated development of antibiotic resistant genes (ARG). Animal handling, waste management, and bioaerosol generation may contribute to relatively high personal exposure to antibiotic resistant bacteria (ARB) on farms. The short- and long-term health effects of these bacteria are currently unknown. Moreover, workers may act as a vector – disseminating ARG and viruses. Specifically, cattle workers are at greater risk of Influenza D virus, an emerging pathogen associated with acute respiratory disease. The workers may also pose a threat to the animals, such as introducing strains of multi-drug resistant tuberculosis (TB). We propose to address critical questions that remain about the impacts of worker exposure to respiratory pathogens and transmission to animals, farms and the larger community. The eighteen year collaborative research program conducted by the High Plains Intermountain Center for Agricultural Health and Safety and regional dairy and beef producers offers a unique opportunity to investigate the role of workplace exposure on human-hosted bacterial communities (microbiome), associated antibiotic resistance genes (ARG, or resistome) and respiratory viruses (virome) and respiratory health in cattle workers. The research objective is to ascertain if ARG and viruses are underlying risk factors for subclinical markers of respiratory inflammation. The central hypothesis is that the nasal microbiome of cattle workers will have distinct microbial communities and genetic constitution that are associated with measurable levels of inflammation and airway resistance as compared to occupational controls and housemates. The specific aims are to: (1) compare and contrast the composition of the microbiome, resistome, and virome among dairy and beef workers; (2) model exposure-response relationships in the context of microbiome, resistome, virome and inflammatory markers and airway resistance among dairy and beef workers; and (3) ascertain subclinical health impacts of shared microbiome, resistome, and virome between occupational and household settings. This project unites scientists with expertise in occupational health and exposure science, epidemiology, microbiology, genetics, and bioinformatics. This study will contribute to greater awareness of workplace exposures and transmission of ARG and emerging viruses among dairy and beef workers.