# Metabolic Adaptation and Pulmonary ceRNA Network Plasticity in Orientallactaga sibirica During Water Deprivation Stress

## TL;DR

This study explores how Siberian jerboas adapt to extreme water shortage by adjusting their metabolism and lung gene expression.

## Contribution

The study reveals a novel ceRNA network in lung tissues that helps small desert mammals conserve energy during water scarcity.

## Key findings

- Siberian jerboas reduced body mass and food intake by 30.3% and 68.1%, respectively, during water deprivation.
- circ_0015576 acts as a ceRNA to regulate Kcnk15 expression by sequestering miR-503-5p.
- Energy conservation in lung tissues is linked to downregulated genes related to cell proliferation and pulmonary function.

## Abstract

Rising global temperatures lead to a continuous increase in the frequency and intensity of extreme weather events, such as droughts and floods, posing serious threats to terrestrial homeotherms. However, adaptive changes in respiratory metabolism and molecular mechanisms in lung tissues of small mammals under extreme water shortage conditions remain unclear. This study hypothesized that small desert mammals can adapt to extreme water shortage environments by regulating the plasticity of lung tissue gene expression and respiratory metabolism. Using 29 wild-caught Siberian jerboas (Orientallactaga sibirica) as subjects, we implemented a 12-day complete water deprivation protocol to simulate extreme aridity. Body weight, food intake, and daily energy expenditure (DEE) were monitored throughout the experiment. Whole-transcriptome sequencing of lung tissues was performed to profile mRNA, circRNA, and miRNA expression, with competitive endogenous RNA (ceRNA) network analysis to explore molecular mechanisms underlying lung adaptation to water deprivation. Over the 12-day water deprivation (WS) period, Orientallactaga sibirica (O. sibirica) exhibited a 30.3% reduction in body mass and a 68.1% decrease in food intake relative to the baseline level. DEE during the peak activity period at the end of the experiment was 12.6% lower in the WS group compared to the control group. In lung tissue, structural integrity-related genes (Mybl2, Ccnb1) were downregulated. A key finding was that circ_0015576 exhibits a significant positive correlation with the potassium channel gene Kcnk15 and a robust negative correlation with miR-503-5p—suggesting that circ_0015576 functions as a competing endogenous RNA (ceRNA) to sequester miR-503-5p and thereby derepress Kcnk15 expression. Core regulatory genes (ApoA4, Dusp15 etc.) were also coordinately downregulated. Collectively, these results indicate that O. sibirica reduces overall energy expenditure, which may be associated with lung gene expression plasticity, such as those related with lung cell proliferation, pulmonary function, and gas exchange efficiency. This metabolic downregulation facilitates energy conservation under severe water scarcity.