**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** BOVINE RESPIRATORY DISEASE (BRD) IS A HIGHLY COMPLEX DISEASE OF CATTLE THAT RESULTS FROM BACTERIAL AND VIRAL EXPOSURE, STRESS AND REDUCED IMMUNE RESPONSE, AND ABRUPT CHANGES IN THE ANIMAL'S ENVIRONMENT. BEEF PRODUCTION SYSTEMS MAKE EVERYDAY DECISIONS WHICH MAY INFLUENCE THE RISK OF BRD DEVELOPMENT IN CATTLE; THIS SPECIFICALLY INCLUDES VACCINATING CALVES AT A YOUNG AGE AND DECIDING HOW CATTLE ARE MARKETED FOR SALE (I.E., DIRECTLY SOLD TO ANOTHER PRODUCER OR SOLD THROUGH AN AUCTION MARKET). WHILE WE UNDERSTAND THE OVERALL DIFFERENCES IN BRD RATES RELATED TO THESE MANAGEMENT DECISIONS, WE DO NOT UNDERSTAND HOW THEY EFFECT THE ANIMAL'S IMMUNE SYSTEM NOR HOW THEY INFLUENCE THE RELATIONSHIP BETWEEN THE IMMUNE RESPONSE AND THE BACTERIAL COMMUNITY IN THE RESPIRATORY TRACT. THEREFORE, THERE IS A CRITICAL NEED TO RESEARCH HOW THESE COMMONLY USED MANAGEMENT STRATEGIES INFLUENCE HOST IMMUNITY AND MICROBIAL POPULATIONS IN CATTLE, WITH FOCUS ON HOW IT RELATES TO BRD DEVELOPMENT. THE HYPOTHESIS OF THIS PROJECT CATTLE MANAGEMENT DECISIONS, RELATED TO REDUCING RISK OF DISEASE, INFLUENCE HOST IMMUNITY, AND PROMPT CHANGES IN THE COMPOSITION OF THE RESPIRATORY MICROBIAL COMMUNITIES, AND CAN BE ASSOCIATED WITH BRD DEVELOPMENT. THE SPECIFIC SCIENTIFIC OBJECTIVES INCLUDE: 1) ANALYZING THE INFLUENCE OF VACCINATION AND MARKETING STRATEGY ON THE IMMUNE SYSTEM THROUGH THE EVALUATION OF BLOOD RNA OVER SEVERAL TIME POINTS THROUGHOUT THE ANIMAL'S LIFE, AND 2) THE DEVELOPMENT AND USE OF SCIENTIFIC TECHNIQUES TO EXAMINE THE DNA AND RNA OF BACTERIA AND VIRUSES FROM THE ANIMAL'S UPPER RESPIRATORY TRACT AND EXPLORE THE RELATIONSHIP IT HAS WITH THE ANIMAL'S IMMUNE RESPONSE AND DEVELOPMENT OF BRD. TO ACCOMPLISH THIS, WE WILL USE PREVIOUSLY-OBTAINED SAMPLES FROM CATTLE HAVING EITHER BEEN VACCINATED OR NOT WITH A COMMERCIALLY-AVAILABLE VIRAL VACCINE AGAINST BRD, DURING THE COW-CALF PHASE OF LIFE, AND HAVE EITHER BEEN DIRECTLY TRANSPORTED OR PLACED THROUGH A COMMERCIAL AUCTION SYSTEM PRIOR TO TRANSPORT TO A BACKGROUNDING OPERATION. SPECIFICALLY, WE WILL ANALYZE THE RNA FROM BLOOD SAMPLES AND THE MICROBIAL DNA AND RNA FROM NASAL SWABS COLLECTED FROM SIX DIFFERENT TIME POINTS THROUGHOUT THE COW-CALF AND BACKGROUNDING PHASE. WE EXPECT THAT THE USE OF COMMERCIALLY AVAILABLE VACCINES AGAINST BRD-ASSOCIATED VIRUSES AND EXPOSURE TO COMMERCIAL MARKETING SYSTEMS, OPPOSED TO DIRECT PURCHASING, WILL INDUCE DISTINCT HOST IMMUNE AND MICROBIAL PATTERNS WHICH CAN BE LEVERAGED TO PREDICT AN ANIMAL'S BACKGROUND AND RISK OF BRD. THE RESULTS OF THIS WORK MAY BETTER OUR UNDERSTANDING OF HOW THESE MANAGEMENT STRATEGIES IMPACT THE IMMUNE SYSTEM AND THE RESPIRATORY MICROBIAL FLORA, ENHANCE OUR BRD PREVENTION AND CONTROL STRATEGIES, AND IMPROVE CATTLE HEALTH OUTCOMES.