Xiao-jun Wang ^1,2 Chutian Zhang ³ Åsa M. Wheelock ⁴ Siming Xin ² Hui Cai ^5* Lei Xu ^6,7* Jing Gao ^1,4,6,8*

• ¹ Department of Respiratory Medicine, Gansu Provincial Hospital, Lanzhou, China
• ² The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou, Gansu Province, China
• ³ College of Natural Resources and Environment, Northwest A&F University, Yangling, China
• ⁴ Respiratory Medicine Unit, Department of Medicine, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Stockholm, Sweden
• ⁵ Gansu Provincial Hospital, Lanzhou, Gansu Province, China
• ⁶ Vanke School of Public Health, Tsinghua University, Beijing, Beijing Municipality, China
• ⁷ Institute for Healthy China, Tsinghua University, Beijing, China
• ⁸ Department of Respiratory Medicine, University of Helsinki, Helsinki, Finland

The coronavirus disease 2019 (COVID-19) pandemic underscores the critical need to integrate immunomics within the One Health framework to effectively address zoonotic diseases across humans, animals, and environments. Employing advanced high-throughput technologies, this interdisciplinary approach reveals the complex immunological interactions among these systems, enhancing our understanding of immune responses and yielding vital insights into the mechanisms that influence viral spread and host susceptibility. Significant advancements in immunomics have accelerated vaccine development, improved viral mutation tracking, and broadened our comprehension of immune pathways in zoonotic transmissions. This review highlights the role of animals, not merely as carriers or reservoirs, but as essential elements of ecological networks that profoundly influence viral epidemiology. Furthermore, we explore how environmental factors shape immune response patterns across species, influencing viral persistence and spillover risks. Moreover, case studies demonstrating the integration of immunogenomic data within the One Health framework for COVID-19 are discussed, outlining its implications for future research. However, linking humans, animals, and the environment through immunogenomics remains challenging, including the complex management of vast amounts of data and issues of scalability. Despite challenges, integrating immunomics data within the One Health framework significantly enhances our strategies and responses to zoonotic diseases and pandemic threats, marking a crucial direction for future public health breakthroughs.