# Advances in Single-Cell Transcriptomics for Livestock Health

## TL;DR

Single-cell RNA sequencing is helping scientists understand immune responses in livestock, leading to better vaccines and healthier animals.

## Contribution

This review highlights the use of single-cell transcriptomics to map immune systems and improve disease resistance in livestock.

## Key findings

- Cell atlases like the Cattle Cell Atlas reveal species-specific immune cell populations in livestock.
- Single-cell sequencing has clarified how pathogens interact with immune cells in different tissues.
- The technology aids in monoclonal antibody discovery and vaccine design for livestock diseases.

## Abstract

Animals such as cattle, pigs, sheep, and goats are essential for global food security, but infectious diseases threaten their health and productivity. Understanding how these animals fight infections has been difficult because traditional laboratory methods cannot distinguish between the many different types of immune cells working together to protect the body. A new technology allows scientists to examine thousands of individual cells one at a time, revealing the complete diversity of immune cell types and how each respond to disease. This review examines recent progress using this technology across major livestock species. Scientists have created detailed cellular maps of healthy animals and discovered how specific cell types respond to important diseases like mastitis in dairy cows and viral infections in pigs. These findings are helping researchers design better vaccines, identify animals with stronger natural immunity for breeding programs, and develop new treatments. This work ultimately supports healthier animals, more sustainable farming, and safer food for consumers worldwide.

RNA sequencing (scRNA-seq) has emerged as a transformative technology for dissecting cellular heterogeneity and immune complexity in livestock species. This review summarizes recent advances in the application of single-cell transcriptomics to livestock health, with a particular focus on immune system organization and host–pathogen interactions in cattle, pigs, poultry, and small ruminants. We highlight the development of large-scale, multi-tissue cell atlases—such as the Cattle Cell Atlas and resources generated through the Farm Animal Genotype-Tissue Expression (FarmGTEx) consortium—that provide foundational reference frameworks for livestock genomics. These atlases have enabled the identification of tissue- and species-specific immune cell populations, clarified cellular tropism of major bacterial and viral pathogens, and revealed distinctive immunological features, including the prominent role of γδ T cells in ruminant immunity. We discuss how single-cell immune receptor sequencing has advanced monoclonal antibody discovery and informed rational vaccine design. Key technical and analytical challenges, including incomplete genome annotations, tissue processing constraints, and cross-platform data integration, are critically assessed. Finally, we outline future directions integrating spatial transcriptomics and multi-omics approaches to further resolve immune function within tissue contexts. Collectively, these advances position single-cell transcriptomics as a central framework for improving disease resistance, vaccine efficacy, and translational research in livestock health.