The immune system is the primary defense animals have against infectious diseases. A key component of this defense, the adaptive immune system, generates antibodies that recognize and neutralize bacteria, viruses, and other pathogens. The repertoire of antibodies an animal can produce is determined by a set of genes that vary considerably across mammalian species, yet this variation is almost poorly describe outside of humans, mice, and cattle. This project will conduct the first systematic comparison of immune genes and antibodies across 60 species of mammals, using state-of-the-art DNA and RNA sequencing technologies. The research team will generate high-quality genome assemblies focused on immune-related genes and expressed antibody repertoires, develop new computational tools to analyze them, and identify patterns that explain why species differ in their capacity to respond to infection. All data, genome assemblies, and software produced by this project will be made freely and publicly available, providing a foundational resource for immunology and disease research for years to come with the potential to facilitate biotechnological advances. The project will also provide meaningful research training for graduate and undergraduate students in computational biology, genetics, and immunology. Graduate students will gain hands-on experience with both laboratory sequencing methods and advanced computational analysis, while undergraduate students will participate in paid summer research positions. The team will also host a working group to establish community standards for comparing immune gene data across species, laying the groundwork for a broader research consortium that will expand this work well beyond the lifetime of this grant and further facilitate biotechnology advances. This project will generate paired datasets of antibody repertoires and germline immunoglobulin (IG) loci across approximately 60 mammalian species. For each species, expressed antibody r