# Transcriptomic Analysis of Skin Tissue Reveals Molecular Mechanisms of Thermal Adaptation in Cold-Exposed Lambs

## TL;DR

This study explores how lambs adapt to cold temperatures by analyzing gene activity in their skin, revealing key pathways involved in cold tolerance.

## Contribution

The study identifies breed-specific and shared molecular mechanisms in cold adaptation among Chinese sheep breeds.

## Key findings

- Cold exposure activated immune and endocrine pathways in both Hulunbuir and Hu lambs.
- The TNF signaling pathway and osteoclast differentiation were enriched in cold-exposed lambs.
- Hulunbuir lambs showed greater wool growth and epidermis thickness in cold conditions.

## Abstract

The ruminant livestock farming regions of China are primarily located in the North, where the climate is characterized by seasonal sub-zero temperatures and large temperature fluctuations that can lead to cold stress. Hair fibers and skin serve as primary insulative layers, playing a crucial role in maintaining body temperature in cold environments, so this study aimed to explore the mechanisms of wool and skin response to a cold challenge in lambs of two breeds of indigenous Chinese sheep, the Hulunbuir and the Hu. Several physiological changes in response to the challenge were measured, with similar patterns observed in both the Hulunbuir and Hu lambs, although the changes were more pronounced in the former breed. At −20 °C, both breeds activated pathways related to the immune and endocrine systems, signal transduction, development, and regeneration. The TNF signaling pathway and osteoclast differentiation exhibited enrichment not only in Hulunbuir-specific differentially expressed genes (DEGs) but also in DEGs shared between breeds. These findings suggest their potential as key regulatory pathways mediating cold adaptation mechanisms in lambs, with implications for improving animal welfare standards and fortifying livestock industry resilience against global climatic perturbations.

Cold stress impacts lamb mortality, welfare, and productivity. Wool and skin insulate lambs, but the mechanisms underlying their response to colder environments remain unclear. Shorn lambs (n = 20) of similar age (8 months), of the Hulunbuir (n = 10; average 34.5 ± 0.70 kg) and Hu (n = 10; average 34.9 ± 0.79 kg) breeds, were raised at the Ecological and Agricultural Experimental Station, Gaolan, Gansu Province, People’s Republic of China (36°13″ N, 103°47″ E), at an altitude of 1780 m above sea level. These lambs were divided into four equal groups: Hulunbuir at −20 °C (HB−20), Hulunbuir at 15 °C (HB+15), Hu at −20 °C (HU−20), and Hu at 15 °C (HU+15). The groups were maintained at these temperatures in temperature-controlled facilities for 38 days. Skin tissues were analyzed with transcriptome sequencing, and selected wool and physiological traits were assessed. The HB−20 lambs had greater wool length growth (1.8 ± 0.13 vs. 1.0 ± 0.46 cm, p < 0.001) and epidermis thickness (20.0 ± 1.20 vs. 14.6 ± 0.87 μm, p = 0.006) but lower hair follicle density (33.6 ± 2.11 vs. 42.7 ± 3.06 per mm2, p = 0.041), rectal temperature (38.1 ± 0.10 vs. 38.8 ± 0.04 °C, p < 0.001), and respiratory rate (15.5 ± 1.08 vs. 24.0 ± 1.89 breaths/min, p = 0.004), compared to the HB+15 lambs. Similar differences in these traits were observed with the Hu lambs at the two temperatures. Transcriptome analyses revealed the activation of pathways related to immune and endocrine systems, signal transduction, and development and regeneration, irrespective of breed at −20 °C. The TNF signaling pathway and osteoclast differentiation may play roles in cold adaptation, as they are associated with differentially expressed genes (DEGs) identified in the Hulunbuir lambs, as well as shared DEGs between both breeds. This study revealed physiological and molecular differences in lambs exposed to lower temperatures and suggests potential targets for improving cold tolerance, welfare, and productivity.