**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** AVIAN INFLUENZA (AI) IS AN ECONOMIC THREAT TO US POULTRY PRODUCTION. WITH THE POTENTIAL OF LOW PATHOGENIC (LP) AI EVOLVING TO HIGHLY PATHOGENIC, INNOVATIVE APPROACHES TO IMPROVE GENETIC RESISTANCE TO LPAI ARE CRITICAL TO GENETIC IMPROVEMENT WHILE MINIMIZING ECONOMIC LOSSES. THE RATIONALE IS UNDERSTANDING GENETIC DETERMINANTS OF LPAI RESISTANCE WILL LEAD TO IMPROVING HOST GENETIC RESISTANCE AND ENHANCE PROTECTION FROM AIV INFECTION. WE HYPOTHESIZE THAT IMMUNE CELL FREQUENCIES IN THE HARDERIAN GLAND (HG) ARE ASSOCIATED WITH AIV INFECTION. THE GREATER AIV RESISTANCE IS A RESULT OF GENETIC DETERMINANT GENE REGULATION. IN AIM 1, WE WILL INVESTIGATE THE IMMUNE RESPONSE OF HGS WITH LPAI AND DETERMINE THE SPECIFIC CELL TYPE RESPONSIBLE FOR AIV RESISTANCE. IN AIM 2, IDENTIFY GENE ELEMENTS OF AIV-ASSOCIATED IMMUNE GENES TO PROVIDE CANDIDATESFOR ELUCIDATING THE MOLECULAR MECHANISM OF HOST LPAI RESISTANCE. THE OUTCOME WILL BE SIGNIFICANT BECAUSE UNDERSTANDING THE GENETIC BASIS OF AIV RESISTANCE WILL BRIDGE THE KNOWLEDGE GAP OF AIV PREVENTION AND PROTECTION, MINIMIZE ECONOMIC LOSSES FROM AI OUTBREAKS AND PROMOTE A MORE SUSTAINABLE POULTRY INDUSTRY.