Is it possible to compile C# project into single-file UMD JavaScript library?

While Blazor provides C#/JS interop, it only works in browsers and is designed for SPA. Microsoft doesn't seem to plan adding support for other scenarios: https://github.com/dotnet/aspnetcore/issues/37910

Is it possible to use C# programs and libraries in JavaScript without dependency on DOM or other environment-specific APIs?

It's possible with a custom build of .NET WebAssembly runtime and environment-agnostic JavaScript wrapper.

Here is a solution that uses such custom build to allow compiling C# project into UMD library, which can be used in browsers, node.js and custom restricted environments, such as VS Code's web extensions: https://github.com/Elringus/DotNetJS

To use it, specify Microsoft.NET.Sdk.BlazorWebAssembly SDK and import DotNetJS NuGet package:

<Project Sdk="Microsoft.NET.Sdk.BlazorWebAssembly">

    <PropertyGroup>
        <TargetFramework>net6.0</TargetFramework>
    </PropertyGroup>

    <ItemGroup>
        <PackageReference Include="DotNetJS" Version="*"/>
    </ItemGroup>

</Project>

To associate a JavaScript function with a C# method use JSFunction attribute. To expose a C# method to JavaScript, use JSInvokable attribute:

using System;
using DotNetJS;
using Microsoft.JSInterop;

namespace HelloWorld;

partial class Program
{
    // Entry point is invoked by the JavaScript runtime on boot.
    public static void Main ()
    {
        // Invoking 'dotnet.HelloWorld.GetHostName()' JavaScript function.
        var hostName = GetHostName();
        // Writing to JavaScript host console.
        Console.WriteLine($"Hello {hostName}, DotNet here!");
    }
    
    [JSFunction] // The interoperability code is auto-generated.
    public static partial string GetHostName ();

    [JSInvokable] // The method is invoked from JavaScript.
    public static string GetName () => "DotNet";
}

Publish the project with dotnet publish. A single-file dotnet.js library will be produced under the "bin" directory. Consume the library depending on the environment:

Browser

<!-- Import as a global 'dotnet' object via script tag. -->
<script src="dotnet.js"></script>

<script>

    // Providing implementation for 'GetHostName' function declared in 'HelloWorld' C# assembly.
    dotnet.HelloWorld.GetHostName = () => "Browser";
    
    window.onload = async function () {
        // Booting the DotNet runtime and invoking entry point.
        await dotnet.boot();
        // Invoking 'GetName()' C# method defined in 'HelloWorld' assembly.
        const guestName = dotnet.HelloWorld.GetName();
        console.log(`Welcome, ${guestName}! Enjoy your global space.`);
    };
    
</script>

Node.js

// Import as CommonJS module.
const dotnet = require("dotnet");
// ... or as ECMAScript module in node v17 or later.
import dotnet from "dotnet.js";

// Providing implementation for 'GetHostName' function declared in 'HelloWorld' C# assembly.
dotnet.HelloWorld.GetHostName = () => "Node.js";

(async function () {
    // Booting the DotNet runtime and invoking entry point.
    await dotnet.boot();
    // Invoking 'GetName()' C# method defined in 'HelloWorld' assembly.
    const guestName = dotnet.HelloWorld.GetName();
    console.log(`Welcome, ${guestName}! Enjoy your module space.`);
})();