BOVINE RESPIRATORY DISEASE (BRD) IS PROBLEMATIC THROUGHOUT THE BEEF INDUSTRY, ESPECIALLY IN THE BEEF CATTLE FINISHING PHASE OF PRODUCTION, CONTRIBUTING TO 70 TO 80% OF FEEDLOT DISEASES AND 40 TO 50% OF FEEDLOT DEATH. CURRENT THERAPEUTIC OPTIONS FOR CONTROLLING AND TREATING BRD IN HIGH-RISK ANIMALS INCLUDE VACCINATING AGAINST SOME OF THE VIRUSES THAT INITIATE THE SYNDROME AND PROVIDING ANTIMICROBIAL TREATMENT TO CONTROL SECONDARY BACTERIAL INFECTIONS, WHICH LEADS TO A WIDESPREAD USE OF ANTIMICROBIALS AND THUS INCREASES THE CONCERNS OF ANTIBIOTIC RESISTANCE. TRADITIONAL CULTURE-DEPENDENT STUDIES OF BRD HAVE FOCUSED ON THE FOUR OPPORTUNISTIC BACTERIAL BRD PATHOGENS INCLUDING MANNHEIMIA HAEMOLYTICA, PASTEURELLA MULTOCIDA, HISTOPHILUS SOMNI AND MYCOPLASMA BOVIS. HOWEVER, THESE BACTERIA HAVE BEEN ISOLATED FROM BOTH HEALTHY AND SICK ANIMALS, RAISING QUESTIONS REGARDING THEIR ROLES IN BRD. THERE IS A PAUCITY OF INFORMATION ON THE STRUCTURE OF THE BOVINE RESPIRATORY MICROBIOME AND ITS ROLE INHEALTH AND DISEASE. THE SLOW SCIENTIFIC PROGRESS IN UNDERSTANDING THE BOVINE AIRWAY MICROBIOME COULD BE ATTRIBUTED TO MANY FACTORS. FOR EXAMPLE, CALVES ENTERING FEEDLOTS ARE OFTEN EXTREMELY HETEROGENEOUS, WITH LITTLE INFORMATION REGARDING THEIR GENETICS, SOURCE, HEALTH HISTORY, DISEASE AND ANTIMICROBIAL TREATMENT, DIET, LIVING ENVIRONMENT, AND COMMINGLING TIMES, WHICH SIGNIFICANTLY CONFOUND MICROBIOME STUDIES. IN ADDITION, THUS FAR MOST STUDIES HAVE USED A MORE INVASIVE NASOPHARYNGEAL SAMPLING APPROACH, WHICH IS LESS IDEAL FOR QUICKLY SAMPLING LARGE GROUPS OF ANIMALS IN LARGE-SCALE EPIDEMIOLOGICAL STUDIES THAN NASAL SWABS.IN THIS STUDY, WE WILL USE THREE COHORTS (N=30 EACH) OF CALVES FROM THREE UNIVERSITY OF ARKANSAS RESEARCH STATIONS WITH A KNOWN BACKGROUND (E.G., GENETICS, DIET, ANTIMICROBIALS, ENVIRONMENT) AND MONITOR THE DYNAMICS OF THEIR NASAL MICROBIOMES AFTER BIRTH, WEANING, SHIPPING, MARKETING, AND ENTERING THE FEEDLOT. THIS UNIQUE LONGITUDINAL DESIGN AND NON-INVASIVE NASAL SWAB SAMPLING WILL ALLOW US TO DEFINE A HEALTHY BOVINE NASAL MICROBIOME, AND EXAMINE HOW THE BOVINE NASAL MICROBIOME CHANGES AFTER SHIPPING, COMMINGLING WITH OTHER ANIMALS AND ADAPTING TO A NEW FEEDLOT ENVIRONMENT. BY FOLLOWING A LARGE NUMBER OF CALVES FROM BIRTH TO FEEDLOT AND CHARACTERIZING CHANGES IN THE NASAL MICROBIOME WE WILL BE ABLE TO IDENTIFY MICROBIOME BIOMARKERS FOR ACCURATE DIAGNOSIS, PROGNOSIS, AND TREATMENT OF BRD. IN ADDITION, WE WILL ALSO COLLECT NASOPHARYNGEAL SWABS AND BRONCHOALVEOLAR LAVAGE FROM A SUBSET OF THESE ANIMALS (N=36). BY COMPARING THE MICROBIOME FROM THREE LOCATIONS OF THE BOVINE RESPIRATORY SYSTEM WE WILL BE ABLE TO DETERMINE IF THE NON-INVASIVE NASAL SWAB COULD BE USED TO REPLACE THE NASOPHARYNGEAL SWABS IN BRD STUDIES. FINALLY, WE WILL EXAMINE THE BACTERIAL-HOST INTERACTIONS IN THE BOVINE AIRWAY AND HOW SUCH INTERACTIONS CORRELATE WITH BRD BY SEQUENCING ALL THE FUNCTIONAL GENES FROM THE HOST AND BACTERIA EXPRESSED DURING BRD (METATRANSCRIPTOME ANALYSIS). CHARACTERIZATION OF THE BIOGEOGRAPHY OF THE BOVINE RESPIRATORY TRACT MICROBIOME AND METATRANSCRIPTOME WILL PROVIDE IMPORTANT INSIGHTS INTO THE PATHOBIOLOGY OF BRD AND WILL EVENTUALLY LEAD TO BETTER STRATEGIES TO MODULATE THE BOVINE RESPIRATORY TRACT MICROBIOME TO IMPROVE ANIMAL HEALTH.